Pseudomonas aeruginosa is an opportunistic bacterial pathogen which produces a number of toxic substances able to cause necrotic central corneal ulcerations. The keratitis produced is among the most rapidly spreading and destructive bacterial disease of the cornea known and may result in blindness. Pseudomonas infections of the cornea commonly occur following corneal trauma or wounds resulting from industrial accidents, in corneal transplants or cataract extractions. In addition, infection occurs in the absence of corneal injury in those debilitated by age or immunosuppression or in a combination of these, and in premature infants. At the present time, there are over twenty million persons using daily wear and extended wear soft contact lenses who may also be at risk. Recent studies in our laboratory have employed several experimental models to study pseudomonas infection of the cornea. From this work we have established a unique classification of the inbred mouse strains employed. Mice that are able to restore corneal clarity within a few days to a few weeks after infection are classed as naturally resistant. On the other hand, most other inbred strains are classed as susceptible since corneal infection leads to perforation and phthisis. These findings strongly indicate that the murine host response to infection is under genetic control. This striking differential response to corneal infection by P. aeruginosa is an important, versatile genetic and immunological tool, for continued study of bacterial infections of the cornea, in order to identify important protective mechanisms that might otherwise remain unknown. Therefore, the ultimate goal of this study is to compare, analyze and quantitate the various humoral and cellular defense and underlying regulatory mechanisms operative in the eyes of naturally resistant and susceptible mice. These studies should provide important clinical information for individuals and those patients who may be at risk for ocular infection with this and possibly other opportunistic pathogens.